This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project involves use of a new method, Multi-wavelength Anomalous Diffraction (MADMAX) using Medium Angle X-ray solution scattering (MADMAX), for the precise measurement of interatomic distances within proteins and other macromolecules in aqueous solution. Our preliminary experiments have shown that anomalous differences can be measured from proteins in solution. Differences from selenium scatter have been observed in solution scattering from the potassium channel, kcsa;differences from iron have been observed in scattering from hemoglobin. The work is supported by an NIH Eureka award (for highly innovative research) to support the development of this technique. Recently, we developed a method for computing wide-angle x-ray solution scattering (WAXS) from atomic coordinate sets using an explicit atom representation of water (Park et al.,2009). This, which requires no fitting of parameters) allows us to calculate WAXS patterns to within experimental error to test models for protein structure. We have now extended that capability to include calculation of the anomalous scattering components of proteins (Bardhan and Makowski, unpublished). This greatly increases the power of MADMAX, allowing us to predict the anomalous differences when there are multiple anomalous scattering atoms in the protein. Currently we are collecting anomalous scattering from selenomethionine-labelled proteins of known structure to determine the power of the method for proteins with 1 or 2 or 6-10 selenium labels.